Reactividad de aminoquinonas frente a electrófilos. Síntesis de análogos de Diazaquinomicina A

Se ha estudiado la reactividad de varias aminoquinonas: 2-aminonaftoquinona, 6-aminoquinolinaquinona, 7-aminoquinolinaquinona, 6-amino-4-metilcarbostirilquinona, 2,6-diaminobenzoquinona, frente a reactivos electrófilos. Las reacciones con dielectrófilos se han empleado para la síntesis de análogos de diazaquinomicina a, un compuesto con actividad antitumoral. Los compuestos sintetizados en esta tesis se han ensayado para probar su actividad como posibles antitumorales, mostrando algunos de ellos un prometedor resultado. Las reacciones con monoelectrófilos han conducido a la síntesis de estructuras pentacenicas y oxacinicas, alguna de las cuales también ha resultado poseer actividad como posibles antitumorale

The Modernisation of William Shakespeare’s Hamlet: Identity and Gender in Iris Murdoch’s The Black Prince

This article reads Iris Murdoch’s The Black Prince (1973) as a retelling of William Shakespeare’s Hamlet (1603), paying special attention to the changes that the original play has gone through in order to render it more apt for a contemporary audience. Even if Murdoch also adapts the male hero, the most interesting changes she introduces are related to gender, since the female figures resembling Ophelia and Gertrude bear little resemblance to their Shakespearean counterparts. Gender is also linked to how the novel is written, especially regarding the narrator and his unreliability. Murdoch’s views on women will thus be juxtaposed to those of her (male) narrator. The rest of Murdoch’s characters are also crafted in Shakespearean fashion, given that almost all of them have a counterpart in the original play

La integración de personas con discapacidad en el mundo laboral (el colectivo sordo en Castilla y León)

No disponibleGrado en Relaciones Laborales y Recursos Humano

Los servicios públicos de empleo y la intermediación laboral

El trabajo trata de analizar la evolución y cambios sucedidos en materia de intermediación laboral en nuestro país, a través de los diversos agentes que se han sucedido o complementado a lo largo de la historia para llevarla a cabo. El eje conductor del trabajo es el Servicio Público de Empleo como gestor principal de la intermediación laboral en España, por lo que se habla del monopolio público del mismo, su posterior apertura al sector privado sin ánimo de lucro, la descentralización del INEM, el traspaso de competencias en materia de intermediación a las Comunidades Autónomas, así como de la apertura a partir de la Ley 35/2010, de 17 de septiembre, al sector privado lucrativo en la Intermediación Laboral, sin olvidar la última reforma laboral de 2012 que otorga mayor cobertura a las Empresas de Trabajo Temporal en esta materia.Grado en Relaciones Laborales y Recursos Humano

Expression of Mutant Dynamin Inhibits Toxicity and Transport of Endocytosed Ricin to the Golgi Apparatus

Endocytosis and intracellular transport of ricin were studied in stable transfected HeLa cells where overexpression of wild-type (WT) or mutant dynamin is regulated by tetracycline. Overexpression of the temperature-sensitive mutant dynG273D at the nonpermissive temperature or the dynK44A mutant inhibits clathrin-dependent endocytosis (Damke, H., T. Baba, A.M. van der Blieck, and S.L. Schmid. 1995. J. Cell Biol. 131: 69–80; Damke, H., T. Baba, D.E. Warnock, and S.L. Schmid. 1994. J. Cell Biol. 127:915–934). Under these conditions, ricin was endocytosed at a normal level. Surprisingly, overexpression of both mutants made the cells less sensitive to ricin. Butyric acid and trichostatin A treatment enhanced dynamin overexpression and increased the difference in toxin sensitivity between cells with normal and mutant dynamin. Intoxication with ricin seems to require toxin transport to the Golgi apparatus (Sandirg, K., and B. van Deurs. 1996. Physiol. Rev. 76:949–966), and this process was monitored by measuring the incorporation of radioactive sulfate into a modified ricin molecule containing a tyrosine sulfation site. The sulfation of ricin was much greater in cells expressing dynWT than in cells expressing dynK44A. Ultrastructural analysis using a ricin-HRP conjugate confirmed that transport to the Golgi apparatus was severely inhibited in cells expressing dynK44A. In contrast, ricin transport to lysosomes as measured by degradation of 125I-ricin was essentially unchanged in cells expressing dynK44A. These data demonstrate that although ricin is internalized by clathrin-independent endocytosis in cells expressing mutant dynamin, there is a strong and apparently selective inhibition of ricin transport to the Golgi apparatus. Also, in cells with mutant dynamin, there is a redistribution of the mannose-6-phosphate receptor

La educación en ciencias sociales en el s.xxi: retos y dificultades

En el momento actual, los profesores de Ciencias Sociales debemos enfrentarnos a diversos retos y dificultades a la hora de desempeñar nuestro trabajo. En los últimos años encontramos diferentes cambios en cuanto a la situación del sistema educativo, la legislación, los avances tecnológicos y las necesidades de los educandos. Como profesores debemos reflexionar sobre este nuevo contexto y desarrollar las estrategias y metodologías que tenemos a nuestra disposición con el fin de superar esas dificultades

Evaluación de la respuesta terapéutica en pacientes con enfermedad artrósica por farmacéuticos comunitarios

Introducción: La artrosis es una enfermedad que origina dolor, rigidez e incapacidad funcional. Actualmente el tratamiento es sintomático, no existen fármacos con capacidad para frenar la enfermedad artrósica, aunque los síntomas que origina se pueden aliviar, permitiendo que el paciente padezca lo menos posible.Objetivos: Evaluar la respuesta terapéutica en pacientes con osteoartrosis desde la farmacia comunitaria.Material y métodos: Estudio cuasi experimental no aleatorizado realizado en farmacias comunitarias de Madrid. Se cumplimentó un cuestionario estructurado recogiendo información sobre el paciente, diagnóstico, medicamentos prescritos, articulaciones afectadas, grado de dolor, estado funcional de la articulación, estado global del paciente e intervención farmacéutica realizada.Resultados: La muestra fue constituida por 141pacientes. Los fármacos incluidos pertenecieron a los grupos N02B (36,1 %), M01A (27,6 %), N02AX (23,4 %), M01AH (14,1 %), M01AX (27,6 %) prescritos para osteoartrosis. Con relación al dolor, 34 (24,1 %) pacientes obtuvieron una reducción del dolor de 20 mm en la EVA, alcanzando la respuesta clínica mínima efectiva. Respecto a la calidad de vida, la actividad más afectada fue la de subir y bajar escaleras, presentado muchísimo dolor al subir y bajar escaleras 58 (41,1 %) sujetos. Detectamos 111 RNM, de los que 61 fueron de inefectividad (54,9 %). La intervención farmacéutica fue ofrecer educación sanitaria en el autocuidado de las articulaciones a 29 (20,5 %) pacientes, recomendar ejercicio físico a 32 (22,7 %), recomendar dieta-ejercicio a 23 (16,3 %), derivar al especialista a 19 (13,4 %), derivar al MAP a 12 (8,5 %).Conclusión: La intervención del farmacéutico comunitario en pacientes con osteoartrosis contribuye a mejorar la efectividad de los tratamientos, mejorando los resultados de salud de los mismos

Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention

Phosphoinositides serve as essential players in numerous biological activities and are critical for overall cellular function. Due to their complex chemical structures, localization, and low abundance, current challenges in the phosphoinositide field include the accurate measurement and identification of specific variants, particularly those with acyl chains. Researchers are intensively developing innovative techniques and approaches to address these challenges and advance our understanding of the impact of phosphoinositide signaling on cellular biology. This article provides an overview of recent advances in the study of phosphoinositides, including mass spectrometry, lipid biosensors, and real-time activity assays using fluorometric sensors. These methodologies have proven instrumental for a comprehensive exploration of the cellular distribution and dynamics of phosphoinositides and have shed light on the growing significance of these lipids in human health and various pathological processes, including cancer. To illustrate the importance of phosphoinositide signaling in disease, this perspective also highlights the role of a family of lipid kinases named phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks), which have recently emerged as exciting therapeutic targets for cancer treatment. The ongoing exploration of phosphoinositide signaling not only deepens our understanding of cellular biology but also holds promise for novel interventions in cancer therapy

Impact of COVID-19 lockdown in telecommunications engineering competency-based alumni ranking

[EN] Higher education, as other social and economic sectors in Spain, was disrupted on 15th March 2020 following health emergency Laws enacted related to COVID-19. Non-presential lecturing was stablished country-wide until the end of the academic year 2019-20, as society was set in lockdown. In this context, it is necessary to evaluate the impact of the mandatory changes implemented in the education paradigm in order to assess the degree of acquisition of general and specific competencies altogether the acquisition of transversal competencies, as an important factor for the alumni career. This paper reports a comprehensive study on the competencies degree of acquisition considering the lockdown scenario in Spain. The results from the last four academic years have been comparatively evaluated in the core subject `Teoría de la Comunicación¿, lectured in the fourth semester of the Telecommunications Engineering Integrated Program (Bachelor and Master) in the Universitat Politècnica de València, Spain, comprising data from 745 alumni. The results indicate that the degree of acquisition of technical competencies in this scenario has been adequate, being marginally better compared to previous academic year, probably due to new lecturing materials prepared. Nevertheless, the acquisition of the transversal competency `analysis and problem solving¿ exhibits degraded results, indicating inhomogeneous acquisition probably due to limitations in the group-based problem-solving practice. The results suggest that specific materials and remote lecturing strategies should be developed and implemented to guarantee adequate acquisition levels.The support by the 2020 Science Parks program from the Consellería de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana, Spain, is acknowledged.Llorente, R.; Rodríguez-Hernández, MA.; Hernandez Franco, CA.; Sastre, J.; Carrión García, A.; Madrigal-Madrigal, J. (2020). Impact of COVID-19 lockdown in telecommunications engineering competency-based alumni ranking. IATED Academy. 9599-9607. https://doi.org/10.21125/iceri.2020.2139S9599960

The balance between fitness advantages and costs drives adaptation of bacteriophage Qβ to changes in host density at different temperatures

IntroductionHost density is one of the main factors affecting the infective capacity of viruses. When host density is low, it is more difficult for the virus to find a susceptible cell, which increases its probability of being damaged by the physicochemical agents of the environment. Nevertheless, viruses can adapt to variations in host density through different strategies that depend on the particular characteristics of the life cycle of each virus. In a previous work, using the bacteriophage Qβ as an experimental model, we found that when bacterial density was lower than optimal the virus increased its capacity to penetrate into the bacteria through a mutation in the minor capsid protein (A1) that is not described to interact with the cell receptor.ResultsHere we show that the adaptive pathway followed by Qβ in the face of similar variations in host density depends on environmental temperature. When the value for this parameter is lower than optimal (30°C), the mutation selected is the same as at the optimal temperature (37°C). However, when temperature increases to 43°C, the mutation selected is located in a different protein (A2), which is involved both in the interaction with the cell receptor and in the process of viral progeny release. The new mutation increases the entry of the phage into the bacteria at the three temperatures assayed. However, it also considerably increases the latent period at 30 and 37°C, which is probably the reason why it is not selected at these temperatures.ConclusionThe conclusion is that the adaptive strategies followed by bacteriophage Qβ, and probably other viruses, in the face of variations in host density depend not only on their advantages at this selective pressure, but also on the fitness costs that particular mutations may present in function of the rest of environmental parameters that influence viral replication and stability